The Sinai Robotic Surgery Trial in HPV-related Oropharyngeal Squamous Cell Carcinoma (SIRS 2.0 Trial)

  • End date
    Jun 5, 2027
  • participants needed
  • sponsor
    Icahn School of Medicine at Mount Sinai
Updated on 4 October 2022


The purpose of this study is to determine whether treatment of HPV-related oropharyngeal squamous cell carcinoma in patients with undetectable postoperative HPV circulating tumor DNA (cfHPVDNA), either with transoral robotic surgery (TORS) alone or combined with reduced doses of radiation and chemotherapy can result in cancer control and survival comparable to those previously reported with standard therapy.

The hope is that with this newer approach, the long-term complications from chemotherapy and radiation can be reduced.


There has been significant increase in the incidence of oropharynx cancer in North America and Europe. It is now understood that there are two dominant carcinogenic pathways for oropharyngeal squamous cell carcinoma. Environmentally related which is caused mainly by smoking and alcohol, and HPV-related oropharyngeal squamous cell carcinoma (HPVOPSCC). HPVOPSCC now accounts for almost 60% of OPC seen in the USA and an increasing fraction of these malignancies in Europe. It has been shown that HPVOPSCC confers an excellent prognosis for intermediate staged disease and this has called into question the rational for aggressive concurrent chemoradiotherapy. High-dose radiotherapy (RT) and chemoradiotherapy (CRT) have substantial impact on local tissues and organ function and result in a significant rate of late mortality and morbidity. Studies are now being designed to reduce the impact of RT and CRT for patients.

Recently, a new test has been developed that measures HPV circulating tumor DNA (cfHPVDNA) in the blood. The test has emerged as a promising biomarker for HPVOPSCC, correlating with both treatment response as well as surveillance for cancer recurrence. Data suggests that a negative test in the surveillance period following treatment is highly sensitive and specific for recurrent disease.

In this trial, the study will be stratifying p16 positive patients with PCR detectable high-risk (HR) HPV DNA or RNA following TORS into risk groups based on final pathology to determine appropriate treatment intensity. Patients with low-risk pathologic disease and undetectable postoperative cfHPVDNA will receive no adjuvant therapy. Patients with high-risk pathologic disease and undetectable postoperative cfHPVDNA will receive de-intensified adjuvant radiation and chemotherapy.

Condition HPV-positive Oropharyngeal Squamous Cell Carcinoma
Treatment cisplatin, Robotic Surgery, De-intensified XRT
Clinical Study IdentifierNCT05419089
SponsorIcahn School of Medicine at Mount Sinai
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

OPSCC with positive p16 immunohistochemistry and HR-HPV DNA or RNA PCR
Detectable baseline cfHPVDNA (greater than or equal to 10 fragments/mL)
Early and intermediate stage (T1N0-2B, T2N0-2B) disease without evidence of distant metastases or gross extranodal extension
Age > 18 years
No previous surgery, radiation therapy, or chemotherapy for head and neck cancer
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Less than or equal to 20 pack year tobacco history with no active tobacco use
Adequate bone marrow, hepatic and renal functions

Exclusion Criteria

Advanced nodal stage (AJCC 7th edition N2C, N3) or surgically unresectable disease or disease that cannot be fully resected, unequivocal radiographic extranodal extension, supraclavicular or matted metastatic disease, >3 radiographic pathologic cervical nodes
Previous or current malignancies at other locations, except for adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, thyroid cancer, prostate cancer treated with surgery/radiotherapy, ductal carcinoma in situ of the breast treated with surgery/radiotherapy, or other cancer curatively treated by surgery and with no current evidence of disease for at least 5 years
Non-high-risk HPV subtype on initial biopsy or final pathology
presence of 5 or more positive nodes, irrespective of size, on final pathology
p16 negative or HPV negative OPSCC as determined by IHC and PCR or ISH, respectively
Undetectable or < 10 copies/mL baseline cfHPVDNA prior to surgery
Autoimmune disease treated with chemotherapy agents, anti TNF agents, or hydroxychloroquine within the last 5 years
Other serious illnesses or medical conditions
Participation in an investigational therapeutic drug trial within 30 days of study entry
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